Mustard Gas-Induced Ocular Surface Disorders: An Update on the Pathogenesis, Clinical Manifestations, and Management

Abstract

Purpose: Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries.

Methods: Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye."

Results: Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging.

Conclusions: MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.

Figure 1.

Acute phase of mustard gas-induced ocular surface disorders. a. Chemosis and conjunctival injection. b. Corneal epithelial sloughing.

Figure 2.

Delayed-onset phase of mustard gas-induced ocular surface disorders. a. Telangiectatic ampulliform leaky vessels with peripheral corneal thinning and lipid deposition. b. A patch of inferior corneal thinning and intrastromal lipid and amyloid deposits. c. Corneal surface irregularity, thinning and peripheral corneal infiltration. d. Peripheral corneal melt (healed) following MGK similar to a Mooren’s ulcer.

Figure 3.

Interpalpebral involvement in MGK.

Figure 4.

Histopathological findings of MGK. a. H&E staining x 400, irregular attenuated epithelium, disruption of Bowman’s membrane, subepithelial amorphous hyalinized material, intrastromal vascular channels, paucity of keratocytes. b. H&E staining x 200, denuded epithelium, multiple vascular channels, degenerated collagen fibers. c. H&E staining x 400, amorphous subepithelial hyalinized material with epithelial islands, disruption of Bowman’s membrane, spheroidal degeneration, paucity of keratocytes.

Figure 5.

Advanced cases of MGK. a. Tarsorrhaphy in a 55-year-old man who was suffering from chronic MGK with severe corneal opacity and conjunctivalization. b. Amniotic membrane transplantation in a 61-year-old man with persistent epithelial defect and peripheral thinning. c. Recurrence of MGK after penetrating keratoplasty showing peripheral corneal thinning.

Figure 6.

Summary of the management of acute ocular injury by mustard gas.

Figure 7.

Summary of the management of chronic ocular injury by mustard gas (NSAID: Non-steroidal anti-inflammatory drugs; VEGF: vascular endothelial growth factor; LSCD: limbal stem cell deficiency).